الدكتور احمد الخولي

Background: There is a great need to discover more drugs with antimycobacterial activities to fight lung cancer and tuberculosis (two of the deadliest diseases worldwide). To our knowledge, the present study is the first to report the antimycobacterial activity of imidazole-fused heterocycles. Objective: Construction of some bis-imidazole fused heterocycles with potential anti-tubercular and/or potent antitumor activities. Methods: A series of bis-imidazole fused derivatives 6-8 and 13-16 was constructed using bis-phenacyl bromide derivative 2 as a synthetic platform. Compound 2 was also used to access bis-quinoxaline 20, bis-benzothiazine derivatives 23, and bis-thiazolopyrimidine derivatives 26. The new bis-imidazole derivatives were evaluated for their anticancer activity against the lung carcinoma cell line (A-549) using Cisplatin as a reference drug. The new compounds were also screened for their anti-tubercular activity against M. tuberculosis (ATCC 25177) using Isoniazid as a reference drug. Results: Among the new bis-imidazole derivatives, three examples showed remarkable antitumor activities while five other compounds showed high antimycobacterial activity. Conclusion: A novel series of bis-imidazole fused heterocycles was developed. Multiple prototypes of this new series showed remarkable anti-tubercular and/or potent antitumor activities.

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Refaie M. Kassab, Sobhi M. Gomha, Zeinab A. Muhammad* and Ahmed S. El-khouly

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Journal: Medicinal Chemistry

Global trials are grappling toward identifying prosperous remediation against the ever-emerging and re-emerging pathogenic respiratory viruses. Battling coronavirus, as a model respiratory virus, via repurposing existing therapeutic agents could be a welcome move. Motivated by its well-demonstrated curative use in herpes simplex and influenza viruses, utilization of the nanoscale zinc oxide (ZnO) would be an auspicious approach. In this direction, ZnO nanoparticles (NPs) were fabricated herein and relevant aspects related to the formulation such as optimization, structure, purity, and morphology were elucidated. In silico molecular docking was conducted to speculate the possible interaction between ZnO NPs and COVID-19 targets including the ACE2 receptor, COVID-19 RNA-dependent RNA polymerase, and main protease. The cellular internalization of ZnO NPs using human lung fibroblast cells was also assessed. Optimized hexagonal and spherical ZnO nanostructures of a crystallite size of 11.50 ± 0.71 nm and positive charge were attained. The pure and characteristic hexagonal wurtzite P63mc crystal structure was also observed. Interestingly, felicitous binding of ZnO NPs with the three tested COVID-19 targets, via hydrogen bond formation, was detected. Furthermore, an enhanced dose-dependent cellular uptake was demonstrated. The obtained results infer a rationale, awaiting validation from further biological and therapeutic studies.

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Mohamed Hamdi, Hend Mohamed Abdel-Bar, Enas Elmowafy, Ahmed El-khouly, Mai Mansour, and Gehanne A.S.

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Journal: ACS Omega Article ASAP

Up to date, there were no approved drugs against coronavirus (COVID-19) disease that dangerously affects global health and the economy. Repurposing the existing drugs would be a promising approach for COVID-19 management. The antidepressant drugs, selective serotonin reuptake inhibitors (SSRIs) class, have antiviral, anti- inflammatory, and anticoagulant effects, which makes them auspicious drugs for COVID 19 treatment. Therefore, this study aimed to predict the possible therapeutic activity of SSRIs against COVID-19. Firstly, molecular docking studies were performed to hypothesize the possible interaction of SSRIs to the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-COV-2) main protease. Secondly, the candidate drug was loaded in lipid polymer hybrid (LPH) nanoparticles to enhance its activity. The studied SSRIs were Fluoxetine hydrochloride (FH), Atomoxteine, Paroxetine, Nisoxteine, Repoxteine RR, and Repoxteine SS. Interestingly, FH could effectively bind with SARS-COV-2 main protease via hydrogen bond formation with low binding energy (-6.7 kcal/mol). Moreover, the optimization of FH-LPH formulation achieved 65.1 ± 2.7% encapsulation efficiency, 10.3 ± 0.4% loading efficiency, 98.5 ± 3.5 nm particle size, and 10.5 ± 0.45 mV zeta potential. Additionally, it improved cellular internalization in a time-dependent manner with good biocompatibility on Human lung fibroblast (CCD-19Lu) cells. Therefore, the study suggested the potential activity of FH-LPH nanoparticles against the COVID-19 pandemic.

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Shaymaa Elsayed Khater, AhmedEl-khouly, Hend MohamedAbdel-Bar, Abdulaziz MohsenAl-mahallawi and Dali

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Journal: International journal of Pharmaceutics